Leptomeningeal disease in neurosurgical brain metastases patients: A systematic review and meta-analysis

Abstract

Background: Leptomeningeal disease (LMD) is a complication distinguished by progression of metastatic disease into the leptomeninges and subsequent spread via cerebrospinal fluid (CSF). Although treatments for LMD exist, it is considered fatal with a median survival of 2-4 months. A broader overview of the risk factors that increase the brain metastasis (BM) patient's risk of LMD is needed. This meta-analysis aimed to systematically review and quantitatively assess risk factors for LMD after surgical resection for BM.

Methods: A systematic literature search was performed on 7 May 2021. Pooled effect sizes were calculated using a random-effects model for variables reported by three or more studies.

Results: Among 503 studies, thirteen studies met the inclusion criteria with a total surgical sample size of 2105 patients, of which 386 patients developed LMD. The median incidence of LMD across included studies was 16.1%. Eighteen unique risk factors were reported as significantly associated with LMD occurrence, including but not limited to: larger tumor size, infratentorial BM location, proximity of BM to cerebrospinal fluid spaces, ventricle violation during surgery, subtotal or piecemeal resection, and postoperative stereotactic radiosurgery. Pooled results demonstrated that breast cancer as the primary tumor location (HR = 2.73, 95% CI: 2.12-3.52) and multiple BMs (HR = 1.37, 95% CI: 1.18-1.58) were significantly associated with a higher risk of LMD occurrence.

Conclusion: Breast cancer origin and multiple BMs increase the risk of LMD occurrence after neurosurgery. Several other risk factors which might play a role in LMD development were also identified.

Keywords: brain metastases; leptomeningeal disease; predictive factors; resection.

Figure 1.

Flow diagram literature search.

Figure 2.

Forest plot of hazard ratios (HR) and 95% confidence intervals (CI) of the risk of leptomeningeal disease (LMD) by (A) breast cancer as primary tumor type, (B) multiple brain lesions, and (C) tentorial location of BM. The gray squares represent the point estimate of each study; the size of the squares is proportional to the weight of the study; horizontal lines show the 95% confidence intervals (CIs); the center of the blue diamond represents the pooled estimate for each category. A) The pooled hazard ratio (HR) for the risk factor breast cancer as primary tumor type is 2.73 (95% CI 2.12–3.52; I² = 0%, p-heterogeneity = 0.93; 5 studies). B) The pooled HR for the risk factor multiple brain lesions is 1.37 (95% CI 1.18–1.58; I² = 0%, p-heterogeneity = 0.92; 4 studies). C) The pooled HR for the risk factor tentorial location of BM is 2.24 (95% CI 0.36–13.75; I² = 48%, p-heterogeneity = 0.15; 3 studies). A P-value for heterogeneity <10% was considered significant.